Boron tribromide → 1-Cyclohexyl-3-(3,5-dichloro-2',6'-difluoro-4'-hydroxy-biphenyl-4-ylmethyl)-pyrrolidin-2-one

HRID 2235215Notes

Reaction equation

[CH:1]1([N:7]2[CH2:11][CH2:10][CH:9]([CH2:12][C:13]3[C:18]([Cl:19])=[CH:17][C:16]([C:20]4[C:25]([F:26])=[CH:24][C:23]([O:27]C)=[CH:22][C:21]=4[F:29])=[CH:15][C:14]=3[Cl:30])[C:8]2=[O:31])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH:1]1([N:7]2[CH2:11][CH2:10][CH:9]([CH2:12][C:13]3[C:18]([Cl:19])=[CH:17][C:16]([C:20]4[C:25]([F:26])=[CH:24][C:23]([OH:27])=[CH:22][C:21]=4[F:29])=[CH:15][C:14]=3[Cl:30])[C:8]2=[O:31])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

Conditions

Temperature: 0 °C

Procedure

Using the procedure to synthesize Example 81 and using reagents 3,5-dichloro-4-((1-cyclohexyl-2-oxopyrrolidin-3-yl)methyl)phenyl trifluoromethanesulfonate (Example 240) (500 mg, 1.0 mmol) and 2,6-difluoro-4-methoxyphenylboronic acid (590 mg, 3.2 mmol) affords 494 mg (100%) of 1-Cyclohexyl-3-(3,5-dichloro-2′,6′-difluoro-4′-methoxy-biphenyl-4-ylmethyl)-pyrrolidin-2-one. Charge a flask with 1-cyclohexyl-3-(3,5-dichloro-2′,6′-difluoro-4′-methoxy-biphenyl-4-ylmethyl)-pyrrolidin-2-one (500 mg, 1.1 mmol), dissolve in dry methylene chloride (10 mL) and cool to 0° C. under nitrogen. Add BBr3 (0.25 mL, 2.7 mmol) and stir at 0° C. for 1.5 hours. Pour into saturated aqueous sodium bicarbonate and extract with methylene chloride. Dry over sodium sulfate, filter and concentrate in vacuo to yield 470 mg (97%) of the title compound.

Workup

extractionextract with methylene chloride
dry with materialDry over sodium sulfate
filtrationfilter
concentrationconcentrate in vacuo

Sources & evidence

ORD record: ord-1abd27b61aa14e4db3a7bb54a9c2adce
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07713979B2

Reaction notes

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